Variant 5-102419906-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_173488.5(SLCO6A1):c.1392A>G(p.Ile464Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLCO6A1
NM_173488.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184

Variant links:

Genes affected

SLCO6A1 (HGNC:23613): (solute carrier organic anion transporter family member 6A1) Predicted to enable sodium-independent organic anion transmembrane transporter activity. Predicted to be involved in sodium-independent organic anion transport. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLCO6A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36471057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO6A1	NM_173488.5 linkuse as main transcript	c.1392A>G	p.Ile464Met	missense_variant	8/14	ENST00000506729.6	NP_775759.3	Q86UG4-1A0A140VJU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO6A1	ENST00000506729.6 linkuse as main transcript	c.1392A>G	p.Ile464Met	missense_variant	8/14	1	NM_173488.5	ENSP00000421339.1		Q86UG4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

244456

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132050

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000554

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456650

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724438

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.1392A>G (p.I464M) alteration is located in exon 8 (coding exon 8) of the SLCO6A1 gene. This alteration results from a A to G substitution at nucleotide position 1392, causing the isoleucine (I) at amino acid position 464 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

T;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.68

.;T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Uncertain

2.4

M;M;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.9

N;N;N

REVEL

Uncertain

0.29

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.24

MutPred

0.64

Loss of catalytic residue at L469 (P = 0.138);Loss of catalytic residue at L469 (P = 0.138);.;

MVP

0.68

MPC

0.52

ClinPred

0.20

GERP RS

1.1

Varity_R

0.27

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over